Stem cells taken from human ovaries were used to produce early-stage eggs by scientists in Boston who may have created a new method to help infertile women.
Females have a fixed number of eggs from birth that are depleted by the time of menopause. The finding, published today in the journal Nature Medicine, challenges the belief that their ovaries can’t make more. The research was led by Jonathan Tilly, the director of Massachusetts General Hospital’s Vincent Center for Reproductive Biology.
Tilly reported in 2004 that ovarian stem cells in mice create new eggs, or oocytes, in a way similar to how stem cells in male testes produce sperm throughout a man’s life. His latest work, if reproduced, would suggest the same is true for human ovaries, potentially pointing at new ways to aid fertility by delaying when the ovaries stop functioning.
“The 50-year-old belief in our field wasn’t actually based on data proving it was impossible, or not ongoing,” Tilly said in a telephone interview. “It was simply an assumption made because there was no evidence indicating otherwise. We have human cells that can produce new oocytes.”
In the study, healthy ovaries were obtained from consenting patients undergoing sex reassignment surgery. The researchers were able to identify ovarian stem cells because they express a rare protein that’s only seen in reproductive cells.
The stem cells from the ovaries were injected into human ovarian tissue that was then grafted under the skin of mice, which provided the blood supply that enabled growth. Within two weeks, early stage human follicles with oocytes had formed.
A female is most endowed with oocytes, or eggs, as a fetus, when she has about 7 million. That number that drops to 1 million by birth, and around 300,000 by puberty. By menopause, the number is zero. Since the 1950’s, scientists thought that ovarian stem cells capable of producing new eggs are only active during fetal development.
“This paper essentially opens the door to the ability to control oocyte development in human ovaries,” Tilly said.
About 10 percent of women of child-bearing age in the U.S., or 6.1 million, have difficulty getting pregnant or staying pregnant, according to the Centers for Disease Control and Prevention. Most cases of female infertility are caused by problems with ovulation, hormone imbalance or age.
The study by Tilley and his colleagues offers “a new model system for understanding the human egg cell,” said David F. Albertini, director of the Center for Reproductive Services and professor in the department of molecular and integrative physiology at Kansas University, in a telephone interview.
Still, “there’s a long way to go before this has real practical applications. I’ve spent 35 years of my life studying egg cells and this is a cell that is at least as complicated as a neuron in the brain, if not more,” Albertini said.
The work needs to be reproduced and expanded by other scientists “to make it into something that will make us confident the cells are safe to use and we could actually use them to repopulate an egg-depleted ovary,” he said.
Tilly’s team is exploring the development of an ovarian stem-cell bank that can be cryogenically frozen and thawed without damage, unlike human eggs, he said. The researchers are also working to identify hormones and other growth factors for accelerating production of eggs from human ovarian stem cells and ways to improve in-vitro fertilization.
“The problem we face with IVF is we don’t have many eggs to work with,” he said. “These cells are renewable. If we are successful -- and it’s a big if -- in generating functioning eggs from these cells, we can generate as many eggs as we need to on a per patient basis.”
Tilly is also collaborating with researchers at the University of Edinburgh in the U.K. to determine whether the oocytes can be developed into fully mature human eggs for fertilizing. The U.S bans creating or fertilizing embryos for experimental purposes, he said.
A company Tilly co-founded, Boston-based OvaScience Inc., has licensed the technology for potential commercial applications. (Bloomberg)
<한글 기사>
불임치료의 길 열리나..줄기세포로 난자 생성
영국-미국 연구팀이 인간의 난소조직에서 채취한 줄기세포를 시험관에서 길러 난자를 만들어내는 데 사상 처음으로 성공했다고 영국의 일간 인디 펜던스 인터넷판이 7일(현지시간) 보도했다.
영국 에든버러 대학과 미국 하버드 대학 공동연구팀은 시험관에서 만든 이 난자가 난자로서의 기능을 갖추고 있는지를 확인하기 위해 정자와 수정을 시도할 것이며 이를 승인해 주도록 영국인간수정배아관리국(HFEA)에 요청할 것이라고 이 신문은 전했다.
에든버러 대학 의과대학의 에블린 텔퍼(Evelyn Telfer) 생식생물학교수는 앞으로 몇 주 안에 HFEA에 공식허가신청서를 제출할 것이라고 밝혔다.
시험관에서 만들어진 난모세포를 정자와 수정시키는 실험은 에든버러 로열병원 체외수정(IVF)센터에서 실시된다.
수정에 성공해 배아가 만들어지면 이 배아는 실험물질로 간주되기 때문에 여성의 자궁에는 주입하지 않고 최장 14일 동안 관찰한 뒤 냉동보존되거나 폐기된다.
이 실험이 성공한다면 불임치료에 획기적인 전기를 가져올 것으로 보인다.
불임여성의 난소조직으로부터 채취한 성체줄기세포를 이용해 시험관에서 난모 세포를 무한정 만들어 낼 수 있기 때문이다.
현재는 배란을 촉진하는 여포자극호르몬을 주입해 난소로부터 적은 수의 성숙된 난자를 직접 채취해 체외수정에 사용한다. 따라서 난자 공급이 쉽지 않은 상황이다.
이 연구에 참가한 미국 하버드 대학의 조너선 틸리(Jonathan Tilly) 박사는 인간의 난소에는 활성화시킬 수 있는 성체줄기세포가 존재하며 따라서 평생 난자의 보충이 가능하다고 밝혔다.
이는 여성은 때 일정한 수의 난모세포를 한꺼번에 가지고 태어나며 이를 평생 이용하다가 폐경과 함께 고갈된다는 생식생물학 기초이론과 배치되는 것이다.
지난 반세기 동안 믿어져온 이 이론은 잘못된 것이라고 틸리 박사는 주장했다.
여성의 난소와 남성의 고환은 난자와 정자로 성숙되는 생식세포 생성 능력이 서로 매치가 되도록 연계되어 있다는 것이 그의 설명이다.
